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miR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos
The microRNAs miR-1 and miR-206 have identical seed sequences and have been reported to regulate angiogenesis in zebrafish by repressing VegfAa expression. Here, Lin et al.describe opposing roles of the two microRNAs in regulating VegfAa expression and therefore angiogenesis in zebrafish.
- Cheng-Yung Lin
- , Hung-Chieh Lee
- & Huai-Jen Tsai
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Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila
During the eversion of Drosophilawing imaginal discs, epithelial cells become migratory in a process similar to the epithelial-to-mesenchymal transition. Here the authors show that the secreted chemoattractant NetrinA promotes epithelial breakdown during disc eversion via downregulation of its receptor Frazzled.
- Rosemary Manhire-Heath
- , Sofia Golenkina
- & Michael J. Murray
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A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality
Nodal signalling has been implicated in the asymmetric positioning of various organs. Here, Noël et al.show that the asymmetry of the embryonic zebrafish heart is also established in the absence of Nodal signalling, suggesting a Nodal-independent mechanism that relies on actomyosin activity.
- Emily S. Noël
- , Manon Verhoeven
- & Jeroen Bakkers
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Hemichordate neurulation and the origin of the neural tube
The evolutionary origins of the chordate neural tube and notochord are unclear. Here the authors show the expression patterns of chordate patterning genes in a hemichordate, which suggest that the hemichordate endoderm and collar cord might be homologous to the chordate notochord and neural tube, respectively.
- Norio Miyamoto
- & Hiroshi Wada
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iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF
The neurotrophic cytokine leukaemia inhibitory factor (LIF) prevents oligodendrocyte death in animal models of multiple sclerosis. Here, Laterza et al. show that secretion of LIF from transplanted iPSC-derived neural progenitor cells has a therapeutic effect in a mouse model of multiple sclerosis.
- Cecilia Laterza
- , Arianna Merlini
- & Gianvito Martino
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| Open AccessSox17 is indispensable for acquisition and maintenance of arterial identity
The transcription factor Sox17 is required for the development of the vasculature in vertebrates. Here Corada et al. show that Sox17 acts downstream of Wnt signalling and upstream of Notch signalling in the regulation of artery and vein differentiation in mice.
- Monica Corada
- , Fabrizio Orsenigo
- & Elisabetta Dejana
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Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis
Loss-of-function mutations in PKD1, the gene encoding the plasma membrane receptor Polycystin-1, lead to renal cyst formation in polycystic kidney disease. Here, Castelli et al. show that Polycystin-1 interacts with the Par3 polarity complex and has a role in the morphogenesis of kidney tubules during mouse development.
- Maddalena Castelli
- , Manila Boca
- & Alessandra Boletta
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Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60
Tip60 is a transcriptional coregulator that has an important role in differentiation. Here, Gao et al. demonstrate that the deubiquitination of Tip60 by USP7, a dominant deubiquitinating enzyme, is a key mechanism in early adipogenesis regulation.
- Yuan Gao
- , Arjen Koppen
- & Eric Kalkhoven
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Gene regulation and priming by topoisomerase IIα in embryonic stem cells
Topoisomerase 2α (Top2α) has essential roles during DNA replication, whereas its isoform Top2β is implicated in gene expression. Thakurela et al.show that Top2α is also required for stem-cell transcriptome regulation and primes developmental genes for activation by Top2β upon terminal differentiation.
- Sudhir Thakurela
- , Angela Garding
- & Vijay K. Tiwari
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Roles of dental development and adaptation in rodent evolution
Tooth shapes vary greatly amongst mammals, but the genetic underpinnings and functional relevance of new dental morphologies are largely unknown. Gomes Rodrigues et al. show that Eda and Edargenes modulate molar crest development in mice, enabling incipient adaptation to highly fibrous diets.
- Helder Gomes Rodrigues
- , Sabrina Renaud
- & Laurent Viriot
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MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation
MBNL and FOX splicing factors are known to have a role in the differentiation of muscle and the nervous system during development. In this study, the authors show that MBNL1 and RBFOX2 regulate alternative splicing of genes that are required specifically for late mesoderm differentiation.
- Julian P. Venables
- , Laure Lapasset
- & Jamal Tazi
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HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA
The nuclear protein HMGB1 is involved in muscle fibre formation. Here, Dormoy-Raclet et al. show that during muscle cell differentiation, the RNA-binding protein HuR promotes HMGB1mRNA translation by preventing its repression by miR-1192.
- Virginie Dormoy-Raclet
- , Anne Cammas
- & Imed-Eddine Gallouzi
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Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal
Wnt/β-catenin signalling can regulate both self-renewal and differentiation of pluripotent stem cells. Here Kim et al.show that transcriptional regulation by nuclear β-catenin induces the differentiation of mouse epiblast stem cells and human embryonic stem cells, whereas cytoplasmic β-catenin supports their self-renewal.
- Hoon Kim
- , Jun Wu
- & Qi-Long Ying
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Environmental impact on direct neuronal reprogramming in vivo in the adult brain
A combination of growth factors and the transcription factor Neurogenin2 has been shown to enhance the production of new neurons from endogenous cells. Here Grandeet al.demonstrate in a rat brain injury model that these factors reprogramme non-neuronal cells into different neuronal phenotypes at distinct efficiencies depending on the environment the cells reside in.
- Andrew Grande
- , Kyoko Sumiyoshi
- & Masato Nakafuku
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MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signalling
The protein MG53 is known to inhibit myogenesis. Here, Ko et al. show that MG53 is an E3 ubiquitin ligase that mediates degradation of insulin receptor substrate 1 in skeletal muscle, thereby regulating myogenesis and insulin sensitivity in vitro and in vivo.
- Jae-Sung Yi
- , Jun Sub Park
- & Young-Gyu Ko
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| Open AccessComplement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration
Components of the complement system have been shown to promote liver regeneration. Haynes et al. demonstrate that the complement fragment C3a can induce regeneration of the embryonic chick retina from stem and progenitor cells of the ciliary margin via activation of STAT3 and other downstream signalling pathways.
- Tracy Haynes
- , Agustin Luz-Madrigal
- & Katia Del Rio-Tsonis
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Bcl-wav and the mitochondrial calcium uniporter drive gastrula morphogenesis in zebrafish
Ca2+ is an intracellular messenger that has a critical role in zebrafish development. Here Prudent et al. show that during gastrulation, the newly identified Bcl-2 homologue, Bcl-wav and the mitochondrial calcium uniporter regulate cell migration by controlling mitochondrial Ca2+storage.
- Julien Prudent
- , Nikolay Popgeorgiev
- & Germain Gillet
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| Open AccessTubular endocytosis drives remodelling of the apical surface during epithelial morphogenesis in Drosophila
During epithelial morphogenesis in Drosophila, the villous apical cell surface is flattened. Fabrowski et al. show that this flattening depends on a dramatic increase in endocytosis associated with the formation of tubular invaginations, revealing a role for membrane trafficking in morphological remodelling.
- Piotr Fabrowski
- , Aleksandar S. Necakov
- & Stefano De Renzis
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Placental programming of anxiety in adulthood revealed by Igf2-null models
Insulin-like growth factor-2 is implicated in foetal and placental development in mammals. Mikaelsson et al. study transgenic mice with disrupted insulin-like growth factor-2 signalling and find that their offspring are more anxious when they reach adulthood.
- Mikael Allan Mikaelsson
- , Miguel Constância
- & Trevor Humby
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DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development
Dipeptidyl-peptidase 6 is implicated in different neuropsychiatric pathologies. Lin and colleagues genetically delete dipeptidyl-peptidase 6 in mice and find that this results in impaired development of dendritic filopodia, as well as a reduction in the dendritic tree size, spine density and functional synapses.
- Lin Lin
- , Wei Sun
- & Dax A. Hoffman
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| Open AccessAngiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms
Angiomotins retain the transcription co-activator YAP in the cytoplasm and thereby regulate the Hippo pathway in mammalian cultured cells. Here Leung and Zernicka-Goetz show that Angiomotin family members prevent the differentiation of inner cell mass cells in the mouse blastocyst, via both Hippo pathway-dependent and -independent mechanisms.
- Chuen Yan Leung
- & Magdalena Zernicka-Goetz
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The RAG2 C-terminus and ATM protect genome integrity by controlling antigen receptor gene cleavage
Mice lacking the C-terminal non-core domain of RAG2 and ATM mutant mice develop thymic lymphomas harbouring recurrentTcra/d–Ightranslocations. Here the authors show that ATM and the non-core domain of RAG2 prevent bi-locus recombination by modulating higher-order chromatin structure.
- Julie Chaumeil
- , Mariann Micsinai
- & Jane A. Skok
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| Open AccessHigh-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics
Systematic large-scale analysis of embryonic development requires the processing of large amounts of microscopy data. Here Schmid et al.solve this problem by developing a high-speed imaging system that projects zebrafish embryos onto a ‘world map’ in real time, revealing characteristic migration patterns in the early endoderm.
- Benjamin Schmid
- , Gopi Shah
- & Jan Huisken
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Changes in the regulation of cortical neurogenesis contribute to encephalization during amniote brain evolution
Reptilian cortical development provides insights into amniote brain evolution. Here, the authors show that cortical neural progenitors in geckoes exhibit limited neurogenic potential, but generate multiple neuron subtypes similar to mammals.
- Tadashi Nomura
- , Hitoshi Gotoh
- & Katsuhiko Ono
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| Open AccesshESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury
Astroglia are heterogeneous in phenotype and not all astrocytes are equivalent in their ability to repair injured brain. Here, the authors show that two defined subtypes of astroglia generated from hESC-derived Olig2-positive versus Olig2-negative neural progenitors, exhibit distinct properties and neuroprotective effects.
- Peng Jiang
- , Chen Chen
- & Wenbin Deng
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The p53–PUMA axis suppresses iPSC generation
Inhibition of the p53–p21 axis increases reprogramming efficiency of somatic cells into induced pluripotent stem cells (iPSCs). Here the authors show that depletion of the pro-apoptotic factor PUMA, acting downstream of p53, increases reprogramming efficiency, providing new insights into the roles of p53 in reprogramming.
- Yanxin Li
- , Haizhong Feng
- & Tao Cheng
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| Open AccessAmplification of progenitors in the mammalian telencephalon includes a new radial glial cell type
Amplification of neural progenitor cells mediates expansion of brain regions. Using imaging of progenitor cell amplification in the mouse ventral forebrain, the authors identify a new progenitor type with high frequency, which they also show to be present in expanded brain regions of other species.
- Gregor-Alexander Pilz
- , Atsunori Shitamukai
- & Magdalena Götz
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| Open AccessThe endoskeletal origin of the turtle carapace
The evolutionary origins of the costal and neural bony plates of the turtle shell have long remained elusive. Here the authors show, through comparative morphological and embryological analyses, that the most of the carapace is derived from endoskeletal ribs.
- Tatsuya Hirasawa
- , Hiroshi Nagashima
- & Shigeru Kuratani
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The ARNT–STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ+CD8αα+ cells
Intraepithelial lymphocytes (IELs) defend against pathogens in the gut, and their differentiation depends on both diet and microbiota-derived factors. Nakajima et al. show that signalling through the aryl hydrocarbon receptor nuclear translocator and STAT3 is required for the development of a subset of IELs.
- Kohei Nakajima
- , Yoichi Maekawa
- & Koji Yasutomo
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| Open Accessα-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors
De novoneurogenesis occurs within the adult hypothalamus, suggesting the existence of a local neural stem cell niche. Here, the authors show that α-tanycytes lining the third ventricle are self-renewing multipotent neural stem cells, whose proliferation is dependent upon local FGF signalling.
- S.C. Robins
- , I. Stewart
- & M. Placzek
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Dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis
Changes in DNA methylation during mammalian spermatogenesis are poorly understood. The authors show that the content of 5-hydroxymethylcytosine, a stable intermediate of DNA demethylation, changes dynamically during mouse spermatogenesis and is associated with functional genomic regions and transcription.
- Haiyun Gan
- , Lu Wen
- & Fuchou Tang
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αTAT1 is the major α-tubulin acetyltransferase in mice
Acetylation of tubulin is proposed to be an important mechanism for the regulation of microtubule stability and diversity. Kalebic et al. generate mice lacking α-tubulin acetyltransferase activity, and reveal that an apparent absence of detectable tubulin acetylation is associated with impaired sperm motility.
- Nereo Kalebic
- , Simona Sorrentino
- & Paul A. Heppenstall
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| Open AccessHaemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21
microRNAs rapidly regulate gene expression and are implicated in cardiogenesis and angiogenesis. Banjo and colleagues show that the microRNA mir-21 is activated by the physical forces generated by blood flow, and that this regulates the development of heart valves in zebrafish.
- Toshihiro Banjo
- , Janin Grajcarek
- & Toshihiko Ogura
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Zscan4 restores the developmental potency of embryonic stem cells
Mouse embryonic stem cells gradually lose their developmental potency in long-term culture. Here the authors show that their deteriorating developmental potency can be restored by transient activation of the Zscan4gene.
- Tomokazu Amano
- , Tetsuya Hirata
- & Minoru S. H. Ko
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TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells
TRF-1 is a telomere-binding protein that protects chromosome ends from degradation. Schneider and colleagues show that TRF1 is a marker of adult stem cell compartments and of induced pluripotent stem cells, and that TRF1 is essential for the induction and maintenance of pluripotency.
- Ralph P. Schneider
- , Ianire Garrobo
- & Maria A. Blasco
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| Open AccessRestricted perinatal retinal degeneration induces retina reshaping and correlated structural rearrangement of the retinotopic map
Development of the visual system involves remodelling of retinal ganglion cell axons. Maiorano and Hindges create a mouse model where specific retinal portions are genetically eliminated, and find that both the retina and its projections reorganize to maintain uniform visual space coverage.
- Nicola A. Maiorano
- & Robert Hindges
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| Open AccessLck tyrosine kinase mediates β1-integrin signalling to regulate Schwann cell migration and myelination
Schwan cells ensheath and insulate axons, enabling efficient transmission of action potentials. Ness and colleagues study the role of the kinase Lck in Schwan cells, and find that Lck signalling regulates cell migration, axonal sorting and myelin thickness.
- Jennifer K. Ness
- , Kristin M. Snyder
- & Nikos Tapinos
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Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii
The Wnt/β-catenin pathway has important roles during neurogenesis in bilaterian animals. The authors show that this pathway regulates the transition from proliferating neural progenitors to differentiating neurons in the annelid Platynereis dumerilii, suggesting a conserved role in the last common bilaterian ancestor.
- Adrien Demilly
- , Patrick Steinmetz
- & Michel Vervoort
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| Open AccessDll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis
Neural stem cells in the adult brain maintain their pool size while producing new neurons. Kawaguchi et al.show that, during neural stem cell mitosis in the adult mouse subventricular zone, the Notch ligand Dll1 is asymmetrically segregated to one daughter cell, which undergoes differentiation.
- Daichi Kawaguchi
- , Shohei Furutachi
- & Yukiko Gotoh
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| Open AccessPAD4 regulates proliferation of multipotent haematopoietic cells by controlling c-myc expression
Histone citrullination by peptidylarginine deiminase 4 (PAD4) regulates transcription but its physiological role is unclear. Here Nakashima et al. show that PAD4 controls proliferation of multipotent haematopoietic cells by modulating c-myc expression.
- Katsuhiko Nakashima
- , Satoko Arai
- & Toru Miyazaki
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A mutation in the receptor Methoprene-tolerant alters juvenile hormone response in insects and crustaceans
Juvenile hormone (JH) is a key regulator of development both in insects and the crustacea Daphnia pulex and D. magna. Here, Miyakawa et al.investigate the evolutionary significance of a single amino-acid variation between crustacea and insects in the JH receptor gene, Methoprene-tolerant.
- Hitoshi Miyakawa
- , Kenji Toyota
- & Taisen Iguchi
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Periodic Wnt1 expression in response to ecdysteroid generates twin-spot markings on caterpillars
Among various pigmentation patterns on caterpillars, sequential spot markings are often used for aposematic colouration. Fujiwara et al. show using genetic and functional analyses that periodic upregulation of Wnt1 in response to ecdysteroid causes twin-spot markings on lepidopteran larvae.
- Junichi Yamaguchi
- , Yutaka Banno
- & Haruhiko Fujiwara
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| Open AccessA sex-specific transcription factor controls male identity in a simultaneous hermaphrodite
Hermaphrodites develop and maintain male and female reproductive organs in a single individual. Chong et al. show that a DM domain transcription factor is required for male germ cell regeneration and maintains ‘maleness’ in a hermaphrodite, the planarian flatworm Schmidtea mediterranea.
- Tracy Chong
- , James J. Collins III
- & Phillip A. Newmark
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An isoform of retinoid-related orphan receptor β directs differentiation of retinal amacrine and horizontal interneurons
Amacrine interneurons act as integrators of visual information in the retina; however the developmental mechanisms that determine this cell fate remain unclear. Liu et al. find that amacrine differentiation in the retina is driven by the transcription factor RORβ1.
- Hong Liu
- , Soo-Young Kim
- & Douglas Forrest
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Article
| Open AccessDeletion of cavin genes reveals tissue-specific mechanisms for morphogenesis of endothelial caveolae
Cavin proteins are key components of mammalian caveolae and are expressed from four genes in a tissue-specific manner. Gram Hansen et al. demonstrate that caveolae in the endothelia of different tissues are remarkably heterogeneous, and reveal a role for cavin 2 in determining the apparent size of cavin complexes.
- Carsten Gram Hansen
- , Elena Shvets
- & Benjamin James Nichols
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Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity
B cells are thought to divide asymmetrically to generate distinct lineages required for adaptive immunity. Hawkins et al. find that surprisingly, mice lacking components of a complex required for asymmetric cell division display normal responses to vaccination and viral infection.
- Edwin D. Hawkins
- , Jane Oliaro
- & Sarah M. Russell
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Dual role of myosin II during Drosophila imaginal disc metamorphosis
The motor protein myosin II is implicated in three-dimensional organ development. In this study, the authors apply live imaging techniques to describe the dynamics of the developing Drosophilawing and the involvement of myosin II in this process.
- Silvia Aldaz
- , Luis M. Escudero
- & Matthew Freeman
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Article
| Open AccessmiR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit
Brown fat can dissipate energy as heat and has an important role in energy homoeostasis of rodents and possibly humans. Chenet al. show that microRNA 155 regulates the differentiation of brown adipocytes as well as the 'browning' of white fat cells in mice.
- Yong Chen
- , Franziska Siegel
- & Alexander Pfeifer
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Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells
Even though both embryonic stem cells and primordial germ cells express pluripotency markers, they differ in their developmental potential. Maeda et al. show that, in embryonic stem cells, the Myc family member Max mediates epigenetic repression of genes involved in germ cell development.
- Ikuma Maeda
- , Daiji Okamura
- & Yasuhisa Matsui
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